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NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting
Cancer Immune Control
#MMPMID29429633
Böttcher JP
; Bonavita E
; Chakravarty P
; Blees H
; Cabeza-Cabrerizo M
; Sammicheli S
; Rogers NC
; Sahai E
; Zelenay S
; Reis e Sousa C
Cell
2018[Feb]; 172
(5
): 1022-1037.e14
PMID29429633
show ga
Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity,
and their abundance within tumors is associated with immune-mediated rejection
and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse
tumors often depends on natural killer (NK) cells that produce the cDC1
chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5,
XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK
cells and cDC1 and are associated with increased overall patient survival.
Notably, tumor production of prostaglandin E2 (PGE(2)) leads to evasion of the NK
cell-cDC1 axis in part by impairing NK cell viability and chemokine production,
as well as by causing downregulation of chemokine receptor expression in cDC1.
Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1
recruitment that is targeted by tumor-derived PGE(2) for immune evasion and that
could be exploited for cancer therapy.
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